The fine detail of a healthy heart

Scientists have taken another step in the quest to create a “Google map of the human body” by putting together a detailed cellular and molecular map of the healthy heart.

An international team analysed almost half a million individual cells and cell nuclei from six different regions of the heart obtained from 14 organ donors whose hearts were healthy but unsuitable for transplantation.

The result is the Heart Cell Atlas, which, shows the huge diversity of cells and reveals heart muscle cell types, cardiac protective immune cells and an intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.

The research, described in the journal Nature, was led by Harvard Medical School and Brigham and Women’s Hospital, US, the Wellcome Sanger Institute and Imperial College London, UK, and the Max Delbrück Centre (MDC) for Molecular Medicine in Germany.

It is part of the Human Cell Atlas initiative to map every cell type in the human body.

“Understanding the healthy heart will help us understand interactions between cell types and cell states that can allow lifelong function and how these differ in diseases,” says Harvard’s Christine Seidman, a co-senior author.

“Ultimately, these fundamental insights may suggest specific targets that can lead to individualised therapies in the future, creating personalised medicines for heart disease and improving the effectiveness of treatments for each patient.”

The researchers used a combination of single-cell analysis, machine learning and imaging techniques to see exactly which genes were switched on and off in each cell.

In these beating human heart cells, scientists have highlighted a protein important in muscle contraction (green). Credit: Seidman Laboratory

They discovered major differences in the cells in different areas of the heart and observed that each area had specific subsets of cells – a finding they say points to different developmental origins and suggests these cells would respond differently to treatments.

“This is the first time anyone has looked at the single cells of the human heart at this scale, which has only become possible with large-scale single-cell sequencing,” says MDC’s Norbert Hübner, a co-senior author.

The researchers also examined blood vessels running through the heart in unprecedented detail. The atlas shows how the cells in these veins and arteries are adapted to the different pressures and locations and how this could help researchers understand what goes wrong in blood vessels during coronary heart disease.

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